von Willebrand factor in factor VIII concentrates protects against neutralization by factor VIII antibodies of haemophilia A patients

Abstract

We investigated the neutralization activity of factor VIII (FVIII) antibodies of 12 haemophilia A patients, acquired during treatment with plasma-derived FVIII concentrates. All plasma samples, drawn in a clinically stable situation before any immunotolerance treatment, contained anti-A2 domain and anti-light-chain FVIII antibodies. In nine patients' plasmas, containing relatively high amounts of FVIII light-chain antibodies (53-96%), a higher neutralization activity was found against recombinant FVIII concentrate (Recombinate) than against plasma-derived von Willebrand factor (vWF)-containing concentrate (Haemoctin SDH). No difference in neutralization of the two concentrates was found in two patients' plasmas with almost equal content of FVIII light- and heavy-chain antibodies, or one plasma with predominantly heavy-chain antibodies. These results suggest that haemophilia A patients with relatively high amounts of FVIII light-chain antibodies in plasma might benefit by infusion of FVIII concentrates containing vWF because vWF appears to have some protective effect on FVIII. This hypothesis should be tested by a clinical study.